The yeast BDF1 gene encodes a transcription factor involved in the expression of a broad class of genes including snRNAs

Lygerou, Zoi; Conesa, Christine; Lesage, Pascale; Swanson, R. N.; Ruet, Anny; Carlson, Marian; Sentenac, André; Séraphin, Bertrand

doi:10.1093/nar/22.24.5332

Cited by 71 publications

(78 citation statements)

References 66 publications

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“…Bdf1 has a domain structure similar to that of other members of the BET family (20). Higher eukaryotic genomes sequenced to date all contain multiple BET members, suggesting that their functions are conserved and important.…”

Section: Discussionmentioning

confidence: 99%

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Bromodomain Factor 1 (Bdf1) Is Phosphorylated by Protein Kinase CK2

Sawa

Nedea

Krogan

et al. 2004

Molecular and Cellular Biology

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Bromodomain factor 1 (Bdf1) associates with Saccharomyces cerevisiae TFIID and corresponds to the C-terminal half of higher eukaryotic TAF1. It also associates with the SWR-C complex, which is important for Htz1 deposition. Bdf1 binds preferentially to acetylated histone H4. Bdf1 is phosphorylated, but the mechanism and significance of this modification have been unclear. Two distinct regions within Bdf1 are phosphorylated; one is just C terminal to the bromodomains and the other is near the C terminus. Mutational analysis shows that phosphorylation is necessary for Bdf1 function in vivo. Endogenous protein kinase CK2 purifies with Bdf1 and phosphorylates both domains. A similar mechanism may be responsible for phosphorylation of the C-terminal region of mammalian TAF1. These findings suggest that CK2 phosphorylation of Bdf1 may regulate RNA polymerase II transcription and/or chromatin structure.Phosphorylation plays an important role in the regulation of transcription by RNA polymerase II (Pol II). The RNA Pol II carboxy-terminal domain (CTD) is phosphorylated by different protein kinases that modulate its interactions with various mRNA processing factors (15). Moreover, the activities of TATA binding protein (TBP) and the TFIIH kinase subunit Kin28 are also regulated by phosphorylation (12). More examples undoubtedly remain to be discovered.The general transcription factor TFIID consists of the TBP and 13 to 14 TBP-associated factors (TAFs) (26). TAFs are involved in promoter recognition and response to some activators. The largest TAF protein (TAF1, formerly known as TAF II 250) has been assigned a variety of activities. Human TAF1 (hTAF1) has been reported to possess two kinase domains that lead to autophosphorylation (5). The protein may also have ubiquitin-activating, conjugating, and acetylase activities that modify histones and basal transcription factors (12,30). Two bromodomains in the C-terminal half of hTAF1 bind to acetylated histones (18,22). TAF1 proteins from higher eukaryotes align with hTAF1 throughout the entire sequence, but Saccharomyces cerevisiae Taf1 corresponds to only the Nterminal half of hTAF1.Yeast bromodomain factor 1 (Bdf1) was identified as a Taf7 (Taf67)-interacting protein, and this interaction mediates its binding to TFIID. Thus, it appears that Bdf1 corresponds to the C-terminal half of higher eukaryotic TAF1 (20). More recently, Bdf1 has also been found associated with the SWR-C complex, which is important for exchange of Htz1 in place of H2A (14,16,24). Bdf1 preferentially binds hyperacetylated histone H4 and is associated with chromatin (18, 22). Bdf1 is not essential for viability as long as cells contain the closely related Bdf2 protein, but cells cannot survive without at least one of the two bromodomain factors (21). After immunoprecipitation from yeast cells, Bdf1 can be phosphorylated by an unknown associated factor. Recombinant Bdf1 purified from bacteria also gets phosphorylated, but this activity is strongly stimulated by incubation with yeast extract (21). Althoug...

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Section: Discussionmentioning

confidence: 99%

“…Thus, it appears that Bdf1 corresponds to the C-terminal half of higher eukaryotic TAF1 (20). More recently, Bdf1 has also been found associated with the SWR-C complex, which is important for exchange of Htz1 in place of H2A (14,16,24).…”

mentioning

confidence: 98%

Bromodomain Factor 1 (Bdf1) Is Phosphorylated by Protein Kinase CK2

Sawa

Nedea

Krogan

et al. 2004

Molecular and Cellular Biology

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“…The high sequence homology is strongly predictive of a conserved evolutionary function for the ET domain. Many different BET family members, including the yeast bdf1/bdf2, Drosophila fs(1)h, and the mammalian Brd2, Brd3, and Brd4 proteins, have been implicated in transcription regulation (11,13,24,27,32). However, only the CTD, present solely in Brd4 and fs(1)h, has been rigorously documented to regulate transcription through its interaction with pTEFb (4,24,56).…”

Section: Proteomic Analysis Of the Brd4-associated Cellular Proteinsmentioning

confidence: 99%

The Brd4 Extraterminal Domain Confers Transcription Activation Independent of pTEFb by Recruiting Multiple Proteins, Including NSD3

Rahman

Sowa

Ottinger

et al. 2011

Molecular and Cellular Biology

481

490

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Bromodomain protein 4 (Brd4) plays critical roles in development, cancer progression, and virus-host pathogenesis. To gain mechanistic insight into the various biological functions of Brd4, we performed a proteomic analysis to identify and characterize Brd4-associated cellular proteins. We found that the extraterminal (ET) domain, whose function has to date not been determined, interacts with NSD3, JMJD6, CHD4, GLTSCR1, and ATAD5. These ET-domain interactions were also conserved for Brd2 and Brd3, the other human BET proteins tested. We demonstrated that GLTSCR1, NSD3, and JMJD6 impart a pTEFb-independent transcriptional activation function on Brd4. NSD3 as well as JMJD6 is recruited to regulated genes in a Brd4-dependent manner. Moreover, we found that depletion of Brd4 or NSD3 reduces H3K36 methylation, demonstrating that the Brd4/NSD3 complex regulates this specific histone modification. Our results indicate that the Brd4 ET domain through the recruitment of the specific effectors regulates transcriptional activity. In particular, we show that one of these effectors, NSD3, regulates transcription by modifying the chromatin microenvironment at Brd4 target genes. Our study thus identifies the ET domain as a second important transcriptional regulatory domain for Brd4 in addition to the carboxyl-terminal domain (CTD) that interacts with pTEFb.One mechanism underlying the regulation of gene expression is the targeting of multiprotein complexes to modified histones, which then alters the chromatin microenvironment to stimulate or inhibit gene expression. The bromodomains and extraterminal (BET) domain family of proteins are characterized by the presence of two conserved domains, the tandem, amino-terminal bromodomains (BDI and BDII), which bind acetylated chromatin, and an extraterminal (ET) domain, whose function is unknown. The BET family is conserved from yeast to mammals and includes Saccharomyces cerevisiae bromodomain factor 1 (bdf1) and bromodomain factor 2 (bdf2), Drosophila melanogaster female sterile homeotic [fs(1)h], and mammalian Brd2, Brd3, Brd4, and testes/oocyte-specific BrdT/ Brd6. In yeast, deletion of bdf1 leads to a reduced growth rate and deletion of both bdf1 and bdf2 is lethal (27). Mutations of fs(1)h cause segmental abnormalities, including missing organs and homeotic transformations in the progeny of mutant females in Drosophila (13). Knockout of Brd4 or Brd2 in mice results in early embryonic lethality (18,21).The BET proteins have been shown to be important players in human disease, including viral infections and cancer. Several different viruses target the individual BET proteins for a variety of purposes but often to regulate viral and cellular transcription (4,7,31,37,41,45,57,60). The papillomavirus E2 proteins bind to Brd4, and some utilize this interaction in tethering the viral genomes to mitotic chromosomes (1,3,57,59). The papillomavirus E2 transcriptional activation functions are also mediated through Brd4 (35,41,42). With regard to human cancer, the Brd4-NUT and Brd3-NUT fusio...

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“…The bromodomain is a conserved sequence that is found in a variety of transcriptional regulatory proteins (43)(44)(45). The predicted secondary structure of the bromodomain includes two strongly amphipathic ␣ helices followed by reverse turns.…”

Section: Sp140 Component Of the Nuclear Bodymentioning

confidence: 99%

Identification and Characterization of a Leukocyte-specific Component of the Nuclear Body

Bloch

Monte

Guigaouri

et al. 1996

Journal of Biological Chemistry

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The nuclear body (NB) is a cellular organelle that is involved in the pathogenesis of acute promyelocytic leukemia and viral infection. The NB is also a target of antibodies in the serum of patients with the autoimmune disease primary biliary cirrhosis. In this study, serum from a patient with primary biliary cirrhosis was used to identify a cDNA encoding a novel component of the NB, a 140-kDa protein designated Sp140. The predicted amino acid sequence of the amino-terminal portion of Sp140 was similar to Sp100, a previously identified NB protein.

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The yeast BDF1 gene encodes a transcription factor involved in the expression of a broad class of genes including snRNAs

Cited by 71 publications

References 66 publications

Bromodomain Factor 1 (Bdf1) Is Phosphorylated by Protein Kinase CK2

Bromodomain Factor 1 (Bdf1) Is Phosphorylated by Protein Kinase CK2

The Brd4 Extraterminal Domain Confers Transcription Activation Independent of pTEFb by Recruiting Multiple Proteins, Including NSD3

Identification and Characterization of a Leukocyte-specific Component of the Nuclear Body

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